Monitoring reproductive cycles and predicting the time of ovulation in mammals is of great importance to human reproduction and the production of livestock and other animals. Means currently available for detecting ovulation, however, have considerable limitations. For example, surgical techniques for detecting ovulation require that incisions be made so the corpus luteum of the ovary can be observed for physical signs of ovulation. Such a procedure is undesirable and has not gained widespread acceptance. Moreover, clinical evaluations , such as monitoring pelvic discomfort or monitoring basal body temperature are not widely accepted because of the imprecision of the methods and their unreliability for predicting ovulation.
Various biochemical and histological methods for detecting ovulation are also available. Cyclic variations in the concentrations of certain hormones appearing in the blood, such as rises in serum estrogen with a rise in luteinizing hormone, are known indicators of impending ovulation in humans. Measuring the glucose concentration in cervical mucosa and measuring salivary alkaline phosphatase levels have also been explored as methods for detecting ovulation. Because of the risk of sample contamination and the amount of technical expertise required to accurately perform necessary collections and analyses, histological and biochemical tests for predicting the occurrence of ovulation often require trained personnel to perform the procedures. Many of these methods, however, remain unreliable in predicting the onset of the fertile period or the occurrence of ovulation.
Vaginal secretions have been monitored for the concentration of volatile organic compounds having a molecular weight between 50 and 350 grams per mole for use as predictors of the fertile period and ovulation. U.S. Pat. No. 3,986,494, "Method of Predicting and Detecting Ovulation", Preti et al., Oct. 19, 1976. The concentration of a particular volatile organic compound, such as acetic or lactic acid, is used to diagnose the occurrence of ovulation in the menstrual cycle. The compounds monitored have a first increase in concentration just prior to the rise in serum estrogens, thereby indicating the onset of the fertile period. At least four days after the first increase, a second increase in the volatile organic compound indicates the time of ovulation. This method is estimated to be useful in accurately predicting the fertile period and ovulation in approximately only 80% of the female human population.
U.S. Pat. No. 4,010,738, "Method of Predicting and Detecting Ovulation", Preti et al., Mar. 8, 1977, discloses monitoring urea concentrations in vaginal secretions of mammals as a method of diagnosing the onset of the fertile period or ovulation. As with other methods known for monitoring various compounds in vaginal secretions, the likelihood of contamination of the secretion with other body secretions or feces is great. Moreover, urea concentration is influenced by nutrition and digestion, and is not a reliable indicator of reproductive cycle events.
Other methods for detecting the onset of the fertile period and ovulation include monitoring the volatile sulfur content of mouth air. U.S. Pat. No. 4,119,089, "Method of Predicting and Determining Ovulation by Monitoring the Concentration of Volatile Sulfur-Containing Compounds Present in Mouth Air", Preti et al., Oct. 10, 1978. The volatile sulfur content of mouth air is believed to be a secondary characteristic which is responsive to elevated levels of female sex hormones. A first marked increase in the concentration of volatile sulfur compounds after menses is reported as being predictive of ovulation. A second marked increase in sulfur concentration is reported to be diagnostic of ovulation. Although detection of volatile sulfur content of mouth air may in some way be correlated to, or at least occurring at similar times with particular periodontal conditions occurring at ovulation, the volatile sulfur content of mouth air may also be influenced by other systemic conditions. Thus, it may not be a reliable predictor of ovulation.
Methods for determining the occurrence of estrus in cattle have also been disclosed. Direct rectal palpation or ultrasonography of the ovaries can be performed, however, it is not a viable choice for use in the field by farmers and dairymen. Similarly, measuring the pulsatile release of luteinizing hormone (LH) in serum is not a practical means for monitoring estrus by livestock producers. Other means for detecting estrus, such as serum or milk progesterone level measurement and electronic conductivity tests of cervicovaginal mucus are not accurate and give only retrospective evaluation of the reproductive cycle.
Cow vaginal secretions may be collected over time to determine a significant increase in the amounts of an indicator compound in the secretions. U.S. Pat. No. 4,467,814, "Method for Detecting Bovine Estrus by Determining Methyl Heptanol Concentrations in Vaginal Secretions", Preti et al., Aug. 28, 1984. The indicator compounds are eight-carbon alcohols such as methyl-1-heptanols, particularly 6-methyl-1-heptanol. Specific quantities of the indicator compounds are reported as indicative of estrus. The high risk of contamination and the requirement that specific quantities of compound be identified, as opposed to monitoring variations in quantities, in order to predict estrus make such a method undesirable for monitoring estrus cycles.
Volatile compounds present in blood have been investigated for use as indicators of estrus. Klemm et al., Blood acetaldehyde fluctuates markedly during bovine estrous cycle, In press, Anim. Reprod. Sci.; Klemm, W. R., Acetaldehyde As a Possible Marker and Predictor of Bovine Estrus, In press, Beef Cattle Research in Texas. The low molecular weight compound acetaldehyde was found to increase a few days before behavioral signs of estrus and decrease markedly on the day of estrus or shortly thereafter. Methods for measuring and monitoring acetaldehyde levels in blood or other humoral fluids would allow estrus and/or ovulation in mammals to be predicted.
There remains a great need for a simple, universally acceptable method for detecting and diagnosing mammalian reproductive cycle phases, particularly the occurrence of ovulation. While the shortcomings of the methods discussed apply for mammalian species; predicting ovulation in human females is even more difficult because there are not clear behavioral signs that ovulation is about to occur.
Accurately identifying the time of ovulation in mammals will dramatically increase the likelihood that fertilization occurs and offspring is produced. In cases of particular human medical concerns, such as infertility, diagnosing the time of ovulation is critical to conception. Accurately predicting ovulation will also enable developing reliable rhythm-type birth control methods for humans.
Predicting the occurrence of estrus and ovulation is economically important to livestock breeders, particularly cattle breeders. In order to increase milk production in dairy cattle, and maximize offspring in both dairy and beef cattle, detection of estrus is required. Detecting and predicting estrus and ovulation is particularly important in dairy herds, where artificial insemination is nearly exclusively used to produce fertilization. Larger dairy herd sizes and rising labor costs further increase the need for a method for easily and accurately detecting estrus. Because bovine estrus (lordosis or standing mating behavior) is short (1-18 hours, mean 4.4 hours), with ovulation occurring at about 12 hours after the onset of estrus, there is a herd management need to develop simple chemical tests for compounds that could serve as biochemical markers and predictors of estrus and ovulation. Identification of one or more compounds in a readily accessible body constituent would be an important step in detecting bovine estrus. The common practice of visual monitoring and measuring blood progesterone as indexes of stage of estrus could then be replaced by a more accurate method for detecting estrus and ovulation.